In the past two decades the frequency and types of life-threatening fungal infections have increased dramatically in immuno-compromised patients. Several factors have contributed to this rise such as the expansion of severely ill and or immuno-compromised patient populations with HIV infection, with chemotherapy induced neutropenia, and receiving immunosuppressive therapy; more invasive medical procedures, such as extensive surgery and the use of prosthetic devices and vascular catheters; treatment with broad-spectrum antibiotics or glucocorticosteroids; and peritoneal dialysis or hemodialysis.
This problem of increased fungal infections is accentuated by the emergence of fungal strains which are resistant to currently used antifungal agents. Major opportunistic fungal pathogens include Candida albicans, Aspergillus, Fusurian spp. Other species of Candida such as C. krusei, C. tropicalis, C. glabrata are major causative agents of candidiasis. Invasive pulmonary aspergillosis is a leading cause of mortality in bone marrow transplant recipients. HIV-infected patients are particularly susceptible to mucosal candidiasis, cryptcoccal meningitis.
Fluconazol is the preferred broad spectrum anti-fungal agent used in treatment of fungal infections. In recent times resistance of Candida albicans the most common cause of mucosal candidiasis in HIV-infected patients, after long-term suppressive therapy, to azoles, particularly fluconazole, is a cause of increasing concern. Resistance to fluconazole in other Candida species and in Cryptococcus neoformans has also been reported. Also, fluconazole appears to be less active against the two emerging Candida species, C. glabratta and C. krusei. Infection with Aspergillus, although not common, is frequently life-threatening, and fluconazole has only moderate activity against this fungi.
This has necessitated the need for new antifungal agents with broad spectrum of antifungal activity, which this invention seeks to provide.